Dynamic pupillometry in a cohort of individuals with type II diabetes mellitus and establishing a relationship between pupillary dysfunction and the severity of diabetic retinopathy.

Abstract

Background: Six hundred and forty-two million people will be living with diabetes mellitus (DM) by 2040. (1) Diabetic retinopathy (DR) accounts for 4.8% of the thirty seven million cases of blindness worldwide. Autonomic dysfunction can precede the microvascular changes in DR. Early detection and timely management of DR is of paramount importance to prevent loss of vision. We used the technique of “dynamic pupillometry” to study the pattern of autonomic dysfunction in different grades of DR, and to determine if there was a correlation between pupillary autonomic dysfunction and the severity of DR.

Study design: A hospital-based cross-sectional study.

Subjects: Adults aged 45-80 years (inclusive) with type II DM, and age-matched control participants were recruited from the Dunedin Hospital Eye Department, and the general public, respectively. Two hundred and eleven participants with type II DM (109 male and 102 female) and seventy age-matched controls (19 male and 51 female) were included in the study. Methods: Dynamic pupillometry was performed using a hand held monocular infrared pupillometer (Neuroptics PLR 2000). Outcome measures were the indices of pupillary parasympathetic function: maximum constriction velocity (MCV); average constriction velocity (ACV); absolute constriction amplitude (ACA) and relative reflex amplitude (RRA), and the indices of pupillary sympathetic function: average dilation velocity (ADV); and 75% re-dilation (recovery) time (T75). These indices were compared across the four study groups: Controls; no DR; mild + moderate non proliferative diabetic retinopathy (NPDR); and severe NPDR + proliferative diabetic retinopathy (PDR). Data analysis: Graph Pad Prism version 7.02 and Microsoft Excel were used for the statistical analysis of the data. Demographic characteristics of the participants were analysed. One-way ANOVA statistical test was used to compare the pupillometry indices across the study groups for normally distributed data and Kruskal Wallis Test was used for non-Gaussian distribution. Comparison of the indices between the two groups was performed using unpaired t-test or Mann Whitney U test.

Results: There were significant differences between the groups with mild to moderate NPDR and the group without any visible signs of DR compared to those with severe NPDR + PDR with regard to the indices of parasympathetic pupillary function i.e. ACA (p<0.01) and RRA (p < 0.01). With regard to the indices of sympathetic pupillary function, ADV was found to be significantly decreased in the severe NPDR + PDR group, compared to the control group, no DR group and mild + moderate NPDR group (p<0.0001 in all the three groups). The recovery time was delayed in the severe NPDR + PDR group as compared to the controls (p = 0.0011) and in those with no DR (p = 0.01). Conclusion: The indices of parasympathetic pupillary function were more significantly affected than the indices of sympathetic pupillary function for all grades of DR, suggesting that the autonomic dysfunction in type II DM more significantly affects the parasympathetic innervation than sympathetic innervation. Another significant finding was that all of the dynamic pupillometry indices were either similar or more affected in the group with no visible signs of DR as compared to that of the mild to moderate NPDR group. This finding suggests that, in general, the pupillary autonomic dysfunction precedes detectable microvascular damage in type II DM. This research provides a framework for the exploration of the pattern of autonomic dysfunction in DR. Further research needs to be carried out to validate the utility of dynamic pupillometry in DR screening. Key words: Diabetic retinopathy, dynamic pupillometry, diabetic autonomic neuropathy, pupillary light reflex.